Differential activation of DNA-PK based on DNA strand orientation and sequence bias

DNA-PKcs and Ku are essential components of the complex that catalyzes non-homologous end joining (NHEJ) of DNA double-strand breaks (DSBs). Ku, a heterodimeric protein, binds to DNA ends and facilitates recruitment of the catalytic subunit, DNA-PKcs. We have investigated the effect of DNA strand orientation and sequence bias on the activation of DNA-PK. In addition, we assessed the effect of the position and strand orientation of cisplatin adducts on kinase activation. A series of duplex DNA substrates with site-specific cisplatin–DNA adducts placed in three different orientations on the duplex DNA were prepared. Terminal biotin modification and streptavidin (SA) blocking was employed to direct DNA-PK binding to the unblocked termini with a specific DNA strand orientation and cisplatin–DNA adduct position. DNA-PK kinase activity was measured and the results reveal that DNA strand orientation and sequence bias dramatically influence kinase activation, only a portion of which could be attributed to Ku-DNA binding activity. In addition, cisplatin–DNA adduct position resulted in differing degrees of inhibition depending on distance from the terminus as well as strand orientation. These results highlight the importance of how local variations in DNA structure, chemistry and sequence influence DNA-PK activation and potentially NHEJ

Exploring the impact of dementia friendly ward environments on the provision of care: A qualitative thematic analysis

Dementia-friendly wards are recent developments to improve care for patients with dementia in acute hospitals. This qualitative study used focus groups to understand the impact of dementia friendly ward environments on nurses experiences of caring for acutely unwell patients with dementia. Qualified nurses and health care assistants working in an acute NHS Trust in England discussed their perceptions and experiences of working in a dementia-friendly ward environment. Four themes developed from the thematic analysis: (1) ‘It doesn’t look like a hospital’: A changed environment, (2) ‘More options to provide person-centred care’: No one size fits all, (3) ‘Before you could not see the patients’: A constant nurse presence and (4) ‘The ward remains the same’: Resistance to change. Recommendations and implementations for practice are discussed

Primordial Circumstellar Disks in Binary Systems: Evidence for Reduced Lifetimes

We combine the results from several multiplicity surveys of pre-main-sequence stars located in four nearby star-forming regions with Spitzer data from three different Legacy Projects. This allows us to construct a sample of 349 targets, including 125 binaries, which we use to to investigate the effect of companions on the evolution of circumstellar disks. We find that the distribution of projected separations of systems with Spitzer excesses is significantly different (P ~2.4e-5, according to the KS test for binaries with separations < 400 AU) from that of systems lacking evidence for a disk. As expected, systems with projected separations < 40 AU are half as likely to retain at least one disk than are systems with projected separations in the 40-400 AU range. These results represent the first statistically significant evidence for a correlation between binary separation and the presence of an inner disk (r ~ 1 AU). Several factors (e.g., the incompleteness of the census of close binaries, the use of unresolved disk indicators, and projection effects) have previously masked this correlation in smaller samples. We discuss the implications of our findings for circumstellar disk lifetimes and the formation of planets in multiple systems.Comment: Accepted for publication by ApJ

The Spitzer c2d Survey of Weak-Line T Tauri Stars. III. The Transition from Primordial Disks to Debris Disks

We present 3.6 to 70 {\mu}m Spitzer photometry of 154 weak-line T Tauri stars (WTTS) in the Chamaeleon, Lupus, Ophiuchus and Taurus star formation regions, all of which are within 200 pc of the Sun. For a comparative study, we also include 33 classical T Tauri stars (CTTS) which are located in the same star forming regions. Spitzer sensitivities allow us to robustly detect the photosphere in the IRAC bands (3.6 to 8 {\mu}m) and the 24 {\mu}m MIPS band. In the 70 {\mu}m MIPS band, we are able to detect dust emission brighter than roughly 40 times the photosphere. These observations represent the most sensitive WTTS survey in the mid to far infrared to date, and reveal the frequency of outer disks (r = 3-50 AU) around WTTS. The 70 {\mu}m photometry for half the c2d WTTS sample (the on-cloud objects), which were not included in the earlier papers in this series, Padgett et al. (2006) and Cieza et al. (2007), are presented here for the first time. We find a disk frequency of 19% for on-cloud WTTS, but just 5% for off- cloud WTTS, similar to the value reported in the earlier works. WTTS exhibit spectral energy distributions (SEDs) that are quite diverse, spanning the range from optically thick to optically thin disks. Most disks become more tenuous than Ldisk/L* = 2 x 10^-3 in 2 Myr, and more tenuous than Ldisk/L* = 5 x 10^-4 in 4 Myr.Comment: 40 pages, 13 figures, 4 tables. Accepted for publication in ApJ on September 20, 201

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO

Measurement of the t t-bar production cross section in the dilepton channel in pp collisions at sqrt(s) = 7 TeV

The t t-bar production cross section (sigma[t t-bar]) is measured in proton-proton collisions at sqrt(s) = 7 TeV in data collected by the CMS experiment, corresponding to an integrated luminosity of 2.3 inverse femtobarns. The measurement is performed in events with two leptons (electrons or muons) in the final state, at least two jets identified as jets originating from b quarks, and the presence of an imbalance in transverse momentum. The measured value of sigma[t t-bar] for a top-quark mass of 172.5 GeV is 161.9 +/- 2.5 (stat.) +5.1/-5.0 (syst.) +/- 3.6(lumi.) pb, consistent with the prediction of the standard model.Comment: Replaced with published version. Included journal reference and DO

Measurement of the Z/gamma* + b-jet cross section in pp collisions at 7 TeV

The production of b jets in association with a Z/gamma* boson is studied using proton-proton collisions delivered by the LHC at a centre-of-mass energy of 7 TeV and recorded by the CMS detector. The inclusive cross section for Z/gamma* + b-jet production is measured in a sample corresponding to an integrated luminosity of 2.2 inverse femtobarns. The Z/gamma* + b-jet cross section with Z/gamma* to ll (where ll = ee or mu mu) for events with the invariant mass 60 < M(ll) < 120 GeV, at least one b jet at the hadron level with pT > 25 GeV and abs(eta) < 2.1, and a separation between the leptons and the jets of Delta R > 0.5 is found to be 5.84 +/- 0.08 (stat.) +/- 0.72 (syst.) +(0.25)/-(0.55) (theory) pb. The kinematic properties of the events are also studied and found to be in agreement with the predictions made by the MadGraph event generator with the parton shower and the hadronisation performed by PYTHIA.Comment: Submitted to the Journal of High Energy Physic